The Feasibility Memo

A feasibility memo is a structured, computational assessment of a single gene-therapy target, assembled from public data. It is designed to answer one question early and defensibly: is this gene and indication worth pursuing, and where are the risks?

The feasibility verdict

Every memo opens with one of three verdicts — feasible, feasible with caveats, or not recommended as designed — followed by any blockers (issues to resolve before committing) and caveats (proceed, but address these). The verdict is a computational go/no-go, not a clinical recommendation.

The six sections

Target Rationale

The disease mechanism, inheritance pattern, and which therapeutic modality fits — with a target-confidence score derived from the causal-gene evidence and approved-therapy precedent.

Guide / Transgene Design

For an editing strategy: ranked guide RNAs with on-target efficiency and off-target specificity. For gene replacement: the transgene cassette, with a single-AAV (~4.7 kb) cargo-fit determination and, where the coding sequence is oversized, the clinically used shortened form (e.g. B-domain-deleted F8, micro-dystrophin).

Off-Target Screen

Candidate off-target sites screened against the GRCh38 reference and tiered HIGH / MEDIUM / LOW by predicted consequence, using cell-type expression and genomic context to flag where genome-wide wet-lab confirmation is warranted.

Vector Recommendation

A delivery vector matched to the target tissue and strategy, with a payload-size check against the vector's capacity.

Dosing Rationale

An indicative dose range anchored to approved-product precedent for the same vector class and route, including the relevant safety ceiling (e.g. the systemic-AAV hepatotoxicity limit).

Regulatory Pathway

An indicative FDA/EMA risk tier, the genotoxicity and biodistribution questions to expect, a likely preclinical study list, and a CMC documentation checklist — to map the road ahead, not to replace an IND-enabling package.

Editing vs gene replacement

The memo adapts to the modality the target calls for. Variant-correction and silencing strategies are presented as genome-editing designs (guides, PAM, editor class). Loss-of-function diseases whose clinical modality is to supply a functional gene copy are presented as AAV transgene addition: the transgene cassette, promoter, and whether it fits a single AAV. The two are never mixed in one memo.

Confidence, traceability, and outputs

Findings carry confidence scores, and their limitations are stated rather than hidden. Each assertion is traceable to a public-data source, so a reviewer can follow any claim back to its evidence. You receive the memo as a PDF and a machine-readable data file suitable for your own pipelines.

What it is not

A memo is a computational feasibility study from public data — a decision aid for early triage. It is not experimental evidence and not an IND-enabling package; every finding requires wet-laboratory confirmation before it informs a clinical decision. For how the assessments are computed, see Methodology & data; for how the engine performs against known programmes, see the validation study.